Constipation is a frequent side effect of many conditions and medications. For example, opioids may lead to constipation since these agents decrease peristaltic activity in the gastrointestinal (GI) tract. Because of the mechanisms involved in opioid-induced constipation, some treatments that may be applicable for common, functional constipation are inappropriate for ambulatory-care patients prescribed opioid analgesics. Also in these patients, the distress of constipation may add to the discomfort already present from pain, and they may decrease or discontinue the opioid to avoid constipation. Therefore, motivating such patients to comply with their opioid therapy also requires an approach for managing constipation.
Constipation is broadly defined as the passage of hard, dry stools less frequently than the patient's usual bowel-habit pattern.
Constipation resulting from opioid use is the most common component of a more general condition called opioid-induced bowel dysfunction, OBD. Signs and symptoms of OBD include dry hard stools, straining during evacuation, incomplete evacuation, bloating, abdominal distension, and retention of the contents of the bowel.
Bulk-forming laxatives are typically not appropriate in opioid-induced constipation because peristalsis is inhibited in these patients so stool softener and bowel stimulants are often used. Some patients may take mild over-the-counter bulk laxatives and fail to mention this to their physician. This can result in painful, colic-like symptoms.
Attempts have been made to solve the problem of opioid-induced constipation. For example, U.S. Pat. No. 6,982,283 discloses a method for treating drug-induced constipation that comprises administering an effective amount of 15-keto-prostaglandin compound to a subject suffering from drug-induced constipation or a subject having a strong possibility of suffering from it. U.S. Pat. No. 8,278,323 describes certain quinolizidine and octahydropyridopyrazine compounds, pharmaceutical compositions, and methods of their use as opioid receptor antagonists for the treatment of opioid-induced constipation. The use of an opioid antagonist effectively reduces the amount of physiologically available opioid. However, the dose that leads to constipation is approximately four-fold less than the dose required for an analgesic response.
Accordingly, it is desirable to develop a novel method of treating constipation, including drug-induced constipation.